FDA pushes for harder evidence in mental health drug trials. Here's what we think
Two weeks ago, a scientific advisory committee to the FDA voted 9 to 2 against the use of MDMA (ecstasy) as an effective treatment for Post Traumatic Stress Disorder. They also recommended against approval of MDMA as a treatment. The news shocked some in the community because the relatively large-scale study showed potentially obvious benefits. The study, by Lykos Therapeutics, showed that 80% of those using MDMA in combination with psychotherapy saw significant improvements compared to the group that didn’t.
The core of the FDA committee’s concern was that:
It was impossible to blind the study as the effect of ecstasy was far too obvious, and
It was impossible to obtain independent, objective measures of a reduction in depression severity from the human therapists involved in the study.
A third concern was that the delivery of the psychotherapy was not controlled, making it unclear whether the study outcome was due to the use of MDMA or the quality of the psychotherapy.
There were other concerns with the protocol in particular regarding patient safety during treatment.
The reason for the reaction of shock by the scientific community is that, despite some of the obvious shortcomings of the Lykos clinical trials, the evidence appeared fairly overwhelming and other clinical trials with similar psychedelics appear to confirm the outcomes.
This has implications for other companies studying psychedelic therapies that the FDA will eventually need to evaluate, including Compass therapeutics in the UK, as well as for specialised clinical research organisations supporting psychedelics clinical trials, such as London-based Clerkenwell Health.
The FDA committee’s opinion has got drug developers in the psychedelic space revisiting their trial design plans to ensure they're not going to make the same mistakes that Lykos made. In particular, they are looking for ways to replace the subjective interpretations of therapists and to control for the variable delivery of therapy in the clinical trials.
Both of these can be addressed with AI. Objective measures of depression, using digital endpoints, have been possible for some time now, and the first approaches are going through clinical trials. And non-verbal face and voice analysis techniques measuring trust, empathy, and rapport coupled with modern LLMs and other natural language processing techniques analysing the linguistic element of a therapy session can be used to grade the quality of the psychotherapy component in mixed psychedelic-psychotherapy treatments.
BLUESKEYE AI already has a product, our B-Healthy Platform that provides non-verbal digital biomarkers for the severity of depression and anxiety specifically for clinical trials. The platform analyses face and voice behaviour locally, and stores only the anonymous behaviour patterns remotely for study analysis. This will go a long way towards combatting the concerns of the FDA.
If this is a problem for you, get in touch now for a demo of the B-Healthy Platform!
Another thought - going beyond clinical trials
It’s good that the FDA is calling for more objective measures and more evidence for treatments. But think about it - why should these concerns only apply to the delivery of clinical trials?
In our opinion, the same concerns apply to the routine diagnosis and treatment delivery of most, if not all, mental health conditions. The FDA committee’s opinion should be a serious wake-up call for healthcare providers and health insurers worldwide. Why does a healthcare provider, such as the NHS, still accept performance reporting by tele-therapy providers using PHQ9, which has well-documented problems? Why do health insurers still wait 3 months for evidence of the effectiveness of treatment now that there are objective measures available? Patients would enjoy better outcomes if healthcare providers and insurers would insist on the use of objective measures.
Note on the next steps by the FDA
The FDA does not have to accept the advisory committee’s opinion, although usually it does. The FDA is expected to issue a decision to approve MDMA as a treatment for PTSD in August this year.